News|Articles|July 4, 2024

Insights on the UK's MHRA International Recognition Procedure

Author(s)Mallikaarjunan R, MBA, Senthamilselvi Pachamuthu, Bhuvaneswari Sivaraman, MPharm

The UK’s Medicine and Healthcare Products Regulatory Agency (MHRA) introduced changes to streamline its drug approval processes.

Following Brexit, the United Kingdom’s (UK’s) Medicines and Healthcare products Regulatory Agency (MHRA) introduced significant changes to its drug approval process. Initially, the European Commission Decision Reliance Procedure (ECDRP) was implemented on January 1, 2021. This process relied on the European Commission's decision through the centralized procedure, which required a positive opinion from the Committee for Human Medicinal Products (CHMP).

However, a new regulation, the international recognition procedure (IRP), took effect on January 1, 2024, superseding the ECDRP. The IRP aims to facilitate collaboration between the MHRA and trusted regulatory partners to better serve health care professionals and patients in the UK. Under this procedure, applicants who have already obtained authorization for a drug from one of MHRA's specified reference regulators can benefit from expedited approval.

The IRP offers 2 distinct pathways, Recognition A and B, each with varying criteria, guidelines, and timelines of 60 and 110 days, respectively (Figure 1). This streamlined process significantly reduces both the time and financial burden associated with drug approval compared to traditional marketing authorization procedures. Essentially, the IRP relies on the approval granted by the reference regulator following the review of new drug applications (NDAs) or biological license applications (BLAs).¹

The implementation of the IRP marks an enhancement in the efficiency and effectiveness of the UK's drug approval process. The details of its benefits, processes, and requirements are discussed below.¹

The Need for MHRA to Implement IRP

The marketing approval for an initial drug application is often considered the most challenging task for a pharmaceutical company. To overcome this tedious approval process, the MHRA has implemented a new procedure aimed at expediting approval for products already marketed in Australia, Japan, Canada, Switzerland, Singapore, the US, and the EU.

The IRP benefits health care professionals, patients, and the pharmaceutical sector by reducing time, cost, and labor, making approval possible in just 60 to 110 days (Figure 2). The IRP integrates and simplifies both the Mutual Recognition/Decentralised Reliance Procedure and the ECDRP under one streamlined process.^1,2

A Breakthrough Case Study

A new formulation of a pre-filled syringe denosumab at 120 mg (Xgeva, Amgen) for the treatment of bone cell degeneration due to bone metastasis and giant cell tumors of bone in adults was approved on February 29, 2024, through the IRP. This approval serves as motivation for the development of the regulatory pathway for initial drug applications. The application was initially submitted to the European Marketing Authorization on January 25, 2024. Approximately 30 days later, the drug entered the UK market.³

Understanding the IRP

The IRP is a procedure designed to expedite the introduction of new medicines into the UK market. It is open to applicants who have received approval for the 'same product' from one of the specified reference regulator countries mentioned by the MHRA (eg, Australia, Japan, Canada, Switzerland, Singapore, United States, and the European Union). The guidance specifies that “the same product must contain similar qualitative and quantitative substances and be in the same pharmaceutical form, from applicants belonging to the same group of companies or holding licenses.”¹

Ensuring Compliance and Streamlining Submission Process

To ensure compliance and streamline the submission process, applicants should:^1,4-6

Obtain a positive opinion from CHMP or Mutual Recognition/Centralised Procedure before filing under IRP.
Complete an online eligibility form 6 weeks before submission to determine eligibility for recognition A or B.
Submit applications through the Human Medicines Portal.
Ensure manufacturing procedures by reference regulators comply with Goods Manufacturing Procedure considerations.
Complete a nitrosamine risk assessment before IRP approval.
Be established in the UK or the EU/European economic area.
Note that a pre-submission meeting is not necessary for submission via IRP, but it can be scheduled upon request.
Submit electronic Common Technical Document (eCTD) modules 2 to 5 in EU format at portal submission.

Regulatory Specifications for Module 1 Structure

Even though the IRP involves the dossiers of the reference regulator’s submission, this procedure is entirely evaluated by the MHRA for approval under the UK market. Hence, it is evident that module 1 in eCTD structure should be submitted according to UK specific guidelines to the agency.¹

Impact on Northern Ireland and Transitional Provisions

In Northern Ireland, from January 1, 2025, the Windsor framework is implemented. Currently, under Britain, products can enter the market only if approved from the EU centralized procedure until the Windsor framework comes into existence (Figure 3). Transitional provisions apply until December 31, 2024.¹

Coping With Stringent Criteria of IRP

The regulations are applicable after the approval is granted to the ‘same drug’ or the ‘same group of companies’ belonging to the reference regulators. Along with those studies and the approved documentations, the drug is submitted to MHRA through IRP. Emergency approvals of the drugs are not eligible under IRP. The IRP enhances collaboration between experts and strict adherence to the requirements of the procedure.¹

A pre-submission meeting is not required for IRP submissions. However, if clarification is needed, a meeting can be requested from the agency.

The approval of a new drug in the UK market typically costs £10 to £12 billion, with a turnaround time of 12 to 15 years. Given the increasing prevalence of multiple comorbidities, there's a growing need for numerous medications to treat illnesses. Certain drugs with targeted mechanisms can improve patient compliance. To bypass the lengthy drug approval process from scratch, the IRP procedure allows the UK market to access innovator drugs approved by reference regulators. This enables the MHRA to grant rapid approval for necessary medicines, enhancing revenue for the organization.

On the immediate horizon, the new regulation is set phase-out the earlier one, however, let’s look at some of the questions that abound.¹

Will my drug on the UK market be affected if it is withdrawn from the reference regulator?

Following MHRA approval under IRP, if the applicant withdraws the drug from the reference regulator's market, they must inform the MHRA of their reasons. However, this withdrawal does not impact market approval in the UK, as MHRA and reference regulator approvals are independent of each other. The MHRA will make decisions to further enhance the safety and efficacy of the drug. IRP functions as a standalone procedure for all initial applications.^1,7

What are the obstacles that could be encountered during IRP recognition assessment?

If an application fails to meet requirements or any objections arise under recognition A, it will automatically convert to recognition B.

If major objections persist without resolution by the time the stop clock reaches day 70 in the recognition B timeline, the timeline changes to the national 210-day procedure (Figure 4).¹

Can the Well-Established Use application be employed for IRP?

The Well-Established Use (WEU) application, which has been well-established in the EU market for almost 10 years, does not require the submission of nonclinical or clinical studies for approval in the UK market. However, the IRP rejects the employment of WEU applications due to their inapplicability to evolving clinical considerations and jurisdiction, with ensured safety and efficacy.^1,6

About The Authors

Mallikaarjunan R, MBA, has over 20 years of experience in regulatory operations and manages Navitas Life Sciences’ regulatory services and technology. He has a rich pharmaceutical, consumer, and medical device portfolio having worked with top 10 pharmaceutical companies across the globe, helping to develop/support regulatory strategies, operational improvement, program management, predictive forecasting, develop automation/RPA, and resource plans to manage the supply and demand of the workforce.

Senthamilselvi Pachamuthu is the senior regulatory associate, regulatory operations, and holds a bachelor’s degree in electrical and electronics engineering. She specializes in submissions across various regions including US, EU, Canada, and UK, and is proficient in preparing eCTD modules for diverse submissions such as Initial, NC-1, Post Approval, and LCM.

Bhuvaneswari Sivaraman, MPharm, is the regulatory SME, regulatory operations, and has completed master’s degree in pharmacy. She has published articles in the field of drug development research in different scientific journals.

Ravi Sharma, MPharm, RAC, RAPS, is a seasoned regulatory leader with over 15 years of experience in leading and managing pharmaceutical innovation and life cycle management projects.

Do you think that my product would be applicable for IRP?

The IRP is applicable for the following types of Marketing Authorisation Applications (MAAs) according to the Human Medicines Regulations 2012 (HMRs):

Regulation 50: Chemical and biological new active substances and known active substances.
Regulations 51, 51A, and 51B: Generic Applications.
Regulations 52, 52A, and 52B: Hybrid Applications.
Regulations 53, 53A, and 53B: Biosimilar Applications.
Regulation 55: New fixed combination product applications.

Traditional Herbal Registrations, Homoeopathic Registrations (Simplified Registration Scheme), and Homeopathic National Rules Authorisations (National Rules Scheme) are excluded from IRP. Bibliographic applications (Regulation 54 of the Human Medicines Regulations) are also not eligible.^1,10

What is scope of IRP for the post authorized products in MHRA?

Product Lifecycle Under IRP

The IRP not only streamlines the initial authorization process but extends its scope to cover post-authorization procedures, thereby embracing the entire product lifecycle. This includes:

Line Extensions. Expanding the range of indications, dosage forms, or routes of administration for an already authorized product.
Variations (Type 1B, Type II). Modifications to the authorized product, such as changes in manufacturing processes, specifications, or labelling.
Renewals. Ensuring continued authorization through the renewal process, maintaining compliance with evolving regulatory standards.

This comprehensive approach ensures that medicinal products, once authorized, can adapt, and evolve in response to changing medical needs and advancements in scientific understanding.^1,10

In conclusion, the implementation of an IRP by applicants marks a significant step forward. With the approval and documentation from reference regulators, drugs approved by reference regulators can swiftly enter the UK market through IRP, fostering advancements in science, market dynamics, and the well-being of patients, companies, and health care professionals. By replacing the ECDRP in the UK and embracing the IRP, a milestone has been achieved. This streamlined approval process and global collaboration epitomize efficient marketing authorization for initial drug applications. It represents a guaranteed method of harmonizing various global regulatory standards under a single, unique procedure, promising a more seamless and standardized approach to drug approval across borders.

Editor's Note: Updated on July 11, 2024.

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